Pyripyropenes are a group naturally occurring compounds, which are produced as secondary metabolites by microorganisms and in particular by several filamentous fungi. This group of compounds have attracted attention, because they show very potent inhibition of Acyl-CoA cholesterol acyltransferase (ACAT) in rat liver microsomes (Journal of Antibiotics (1996), 49 (3), 292-298) and have insecticidal activity against several insects, for example, against Helicoverpa armigera larva (Applied and Environmental Microbiology (1995), 61 (12), 4429-4435), Diamondback moth larva (W02004/060065), Tenebrio molitor (W02004/060065) and aphids (W02006/129714).
Up till now, the chemical synthesis of pyripyropenes remains quite difficult, so that a large proportion of pyripyropenes is still produced via fermentation of microorganisms. Microorganisms having the capacity to produce pyripyropenes are for instance Penicillium coprobium PF-1169 strain (Journal of Technical Disclosure No. 500997/2008), Aspergillus fumigatus IF0-1289 strain (Japanese Patent Laid-Open Publication No. 360895/1992), Eupenicillium reticulosporum NRRL-3446 strain (Applied and Environmental Microbiology (1995), 61 (12), 4429-4435), Penicillium griseofulvum F1959 strain (W02004/060065), as well as, Aspergillus fumigatus FO1289 and its mutant Aspergillus fumigatus FO1289-2501. Quite often these microorganisms, e.g. Aspergillus fumigatus FO1289 and its mutant Aspergillus fumigatus FO1289-2501 produce not only one, but several different pyripyropenes which differ in structures of their side chains (Journal of Antibiotics (1996), 49 (3), 292-298). Research in the area of pyripyropenes have not only let to the identification of pyripyropene producing microorganisms and the identification of different kinds of naturally occurring pyripyropenes, but have also provided a phletora of derivatives of pyripyropenes produced via chemical modification of naturally occurring ones. Examples of these derivatives as well as their production processes are disclosed in EP1889540, EP2119361, EP2186815 and EP2426124.
Harvesting the full potential of this interesting group of natural compounds and their derivatives will require the use of effective large scale production methods of pyripyropenes. However, production of pyripyropenes via fermentation of microorganisms and their collection via extraction from the produced biomass still suffers of technical problems and high costs caused during handling and storage of the produced biomass and/or connected to the handling of large volumes during and after extraction of pyripyropenes from the biomass. Technical problems of particular importance are for example a lack of means for long term storage of the produced biomass and the occurrence of high filter resistances during extraction of pyripyropenes from large volumes of biomass.
The present invention results in part from the discovery that it is possible to isolate pyripyropenes from dry biomass without suffering a negative influence on the yield of extracted pyripyropenes in comparison to extractions from non dried material. While at the same time the production of dry biomass and its use for extraction of pyripyropenes dramatically enhanced stability during storage of the biomass, reduces the processed volumes, results in low filter resistance during extraction of pyripyropenes and leads to higher concentrations of pyripyropenes after extraction.